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Aldose reductase gene is associated with diabetic macroangiopathy in Japanese Type 2 diabetic patients

A Watarai1, E Nakashima, Y Hamada

  • 1Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Diabetic Medicine : a Journal of the British Diabetic Association
|August 17, 2006
PubMed
Abstract

Insights

Genetic variations in the aldose reductase (AR) gene, specifically the CT or TT genotype, are linked to an increased risk of stroke in Type 2 diabetic patients. This finding may aid in developing future stroke prevention strategies.

Area of Science:

  • Genetics
  • Metabolic Disorders
  • Cardiovascular Disease

Background:

  • The aldose reductase (AR) gene is crucial in the polyol pathway and has been linked to diabetic microangiopathy.
  • The association between AR gene variations and diabetic macroangiopathy, particularly stroke, remains under-investigated.
  • Understanding genetic predispositions can inform personalized medicine approaches for diabetes complications.

Purpose of the Study:

  • To investigate the association between genetic variations in the aldose reductase (AR) gene and susceptibility to diabetic macroangiopathy.
  • Specifically, to determine if AR gene polymorphisms influence the risk of stroke in Type 2 diabetic patients.
  • To explore the relationship between AR genotype and AR protein levels in erythrocytes.

Main Methods:

  • Genotyping of a single nucleotide polymorphism (C-106T) in the promoter region of the AR gene in 378 Type 2 diabetic patients.
  • Measurement of erythrocyte aldose reductase (AR) protein content using ELISA.
  • Statistical analysis, including logistic regression, to assess the association between AR genotype and stroke risk, adjusted for clinical factors.

Main Results:

  • No significant association was found between AR gene polymorphisms and ischaemic heart disease.
  • A significant increase in the frequency of the CT + TT genotype and T allele of the AR gene was observed in patients with stroke.
  • Erythrocyte AR protein content was elevated in individuals with the CT and TT genotypes compared to the CC genotype, with the association between AR genotype and stroke remaining significant after multivariate adjustment.

Conclusions:

  • The CT or TT genotype of the aldose reductase (AR) gene may serve as a genetic marker for stroke susceptibility in Type 2 diabetic individuals.
  • These findings could contribute to the development of targeted strategies for stroke prevention in diabetic populations.
  • Further research is warranted to elucidate the precise mechanisms linking AR gene variations to stroke risk.

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